Necrotizing fasciitis in neonates: A case report and review of literature

Key Clinical Message Early recognition and treatment of necrotizing fasciitis reduce mortality rate which is 24.1% among neonates. Antibiotics and debridement are common treatments. Hyperbaric oxygen and negative pressure wound healing show potential but need further investigation.


| INTRODUCTION
Necrotizing fasciitis (NF) is a rare fatal rapidly progressive infection that destroys all skin layers and muscles. 1 Due to nonspecific signs and symptoms, it may be misdiagnosed as cellulitis. 2,3Prompt diagnosis and timely treatment are important factors in morbidity and mortality rates. 4The treatment includes broad-spectrum antibiotic and surgical interventions. 5There is little information about NF in neonates; most published articles are case reports.We aimed to present a neonate with NF and then review articles in this age group with a focus on risk factors, signs and symptoms, microbial agents, treatment, and outcome.

| CASE PRESENTATION
A 10-day-old girl presented with an erythematous lesion, with warmness and induration, in the abdomen.She was born at 34 weeks gestational age from a 31-year-old mother.The pregnancy was uneventful, except for intrauterine growth restriction (IUGR) and fetal distress which was the main reason for the preterm termination of the pregnancy with cesarean section.Her first-and fifth-minute Apgar scores were 8 and 9, respectively.Growth indicators included a birth weight of 1250 g, a height of 43 cm, and head circumference of 28 cm.She was admitted to the neonatal intensive care unit due to prematurity, IUGR, and respiratory distress syndrome.She received oxygen for 1 day.Ampicillin and amikacin were started for her.After 3 days, when the blood culture was negative, we discontinued the antibiotics.
On the 10th day, she presented with an erythematous lesion on the abdominal wall, the right side of the umbilicus, with no sign of omphalitis (Figure 1), which changed to necrosis rapidly.The patient had no umbilical line.Vancomycin (10 mg/kg/dose q12h), meropenem (20 mg/ kg/dose q8h), and metronidazole (7.5 mg/kg/dose q24h) started for her, debridement, and irrigation were done via two parallel vertical incisions (Figure 1) with the diagnosis of necrotizing fasciitis continued by daily dressing with gentamycin.
The wound and blood culture were negative.On the 22nd day, she developed feeding intolerance, bilious drainage, and abdominal distension.As she had metabolic acidosis and severe restlessness, with the suspicion of volvulus or obstruction, an exploratory laparotomy was performed.She had normal small bowel, no sign of volvulus, and no thickening of the bowel loops.After 2 days, feeding started in a small amount.Another wound culture was sent that was Acinetobacter sensitive to colistin.Thus, we started colistin.She was in good condition, could tolerate feeding, and the healing site of incisions for NF was obvious.The next wound culture was negative.On the 27th day, she received packed red blood cell due to hematocrit 22.1 and need for oxygen.After that, she had no need to oxygen.On the 30th day, she became tachycardic (heart rate of 180) and on the next day, she developed tachypnea, retraction, hypotension, and lethargy.She was intubated.Pulmonary hemorrhage was obvious.Laboratory data were in favor of sepsis (C-Reactive protein >100, WBC 1.6, Hb 8.8, PLT 70, neutrophil 33%).Unfortunately, she died.

| DISCUSSION
As necrotizing fasciitis is rapidly progressing, delay in diagnosis and treatment is associated with severe morbidities and mortality.Here, we present a neonate who was a case of necrotizing fasciitis; then based on the search on Google Scholar and PubMed with the keywords, newborn, necrotizing fasciitis, and by excluding reports articles the full texts of which were not available, we collected 76 newborn cases and investigated their presentation, risk factor, treatment, and outcome in this age group (Table 1).
The site of involvement was reported in 75 cases.Back was the most frequent site of involvement.In a pediatric systematic review, the lower extremity was reported as the most frequently involved site. 5Hsieh et al. in a neonatal review article reported the abdomen as the most frequent site of involvement and omphalitis as the most associated factor. 30The other sites are shown in Table 2.
The most frequent clinical presentations were erythema, fever, swelling, lethargy, irritability, and blister or lesion (Figure 2).Among all the neonates in our review, the underlying cause was found in 36 neonates.Dirty cord management and fetal scalp monitoring were the most frequent causes (each one in four neonates).Intravenous line complication, circumcision, and NEC each had occurred in three neonates.The others were varicella in siblings, mother's pregnancy complications (PROM, HIV, GBS), environmental factors (lying in the park, insect bite), human interventions (rectal thermometer, head shaving, piercing, surgery, and vaccination), and immunodeficiency (AML, chemotherapy, LADS).In our case, we did not find any underlying cause.
To diagnose NF, we should consider it in patients with soft tissue infection (redness, swelling, warmth) and signs of systemic illness (fever, instability) along with crepitus and rapid progression.The diagnosis is confirmed through surgical exploration in the operating room, involving a thorough examination of the skin, subcutaneous tissue, fascial planes, and muscle. 66olymicrobial infections are the cause of most NFs.The major cause of monomicrobial agents is reported Streptococcus pyogenes (group A streptococcus), a gram-positive bacteria. 67In the pediatrics review, Streptococcus and Staphylococcus were the most common pathogens. 5In our neonatal literature review, staphylococcus aureus was the most monomicrobial     68 Table 3 shows the prevalence of organisms based on our review among neonates.Fungal necrotizing fasciitis can occur in different situations, especially after intramuscular injection and traumatic wounds. 69It is not as prevalent as bacterial agents.In a pediatric review, it was responsible just for one infant. 5We should consider fungal infections, especially when recovery is not achieved by antimicrobial agents. 69he management of NF involves prompt and thorough surgical exploration and removal of necrotic tissues, along with the use of broad-spectrum empirical antibiotics and the provision of hemodynamic support.Administrating antibiotic treatment without performing debridement is linked to a nearly 100% mortality rate. 70Hyperbaric oxygen therapy has received much attention recently. 71

T A B L E 1 (Continued)
T A B L E 2 The site of involvement of necrotizing fasciitis in neonates.procedure, the receives 100% oxygen for a specified time and at a determined pressure.Hyperbaric oxygen therapy for necrotizing fasciitis is controversial, but survival and successful treatment were achieved in some studies. 72,73Negative pressure wound healing is another procedure in which healing occurs by reduced edema, infection, and increased blood flow. 74In our review of the neonates, antibiotic therapy, debridement, skin graft, hyperbaric oxygen, IVIG, and GCSF were used.Table 4 shows the uncommon treatments and mortality based on our review.In our literature review among neonates, vancomycin was the most widely used antibiotic.The other frequently used antibiotics are clindamycin, gentamycin, metronidazole, and meropenem, respectively.In most of the patients, a combination of antibiotics for covering gram-positive, gram-negative, and anaerobes were used.

Site of involvement
There were seven kinds of dressing used in neonates including honey, silver, solcoseryl, Alginate, gentamycin, Mepitel and Acticoat, and iodine.The most prevalent one was honey with a successful outcome.All the neonates for whom honey dressing was used survived (four neonates).Honey was mentioned as a debriding agent with antimicrobial effects in some literature for NF. 75he mortality rate was 24.1% in our review.Gangopadhyay et al. reported 20% mortality in their study of 15 neonates. 76In another report, the mortality rate was 18.2% among 11 neonates. 68In the review article of Hsieh et al., 39 out of 69 neonates died (56.5%). 30In pediatric cases, it was reported 15.4%. 5

| CONCLUSION
Although necrotizing fasciitis is fatal and life-threatening, by early recognition and appropriate treatment, mortality and morbidity rates are decreased.NF is suspected based on clinical signs, including erythema, warmth, and edema, often accompanied by systemic symptoms.Rapid progression is a hallmark feature of this condition.Surgical exploration is essential for both confirming the diagnosis and providing the treatment.Antibiotic therapy and debridement are the most frequently used treatment.Hyperbaric oxygen and negative pressure wound healing are effective treatments in some cases and need further investigation.Further studies are needed in neonates to investigate the risk factors, manifestations, and treatments of NF as there is limited research on innovative treatments in this population.Materials and data provided in this case study are available from the corresponding author on reasonable request.

ETHICAL APPROVAL AND CONSENT TO PARTICIPATE
The publication of this case was approved by the Ethics committee of Shiraz University of Medical Sciences.Written informed consent was obtained from the patient's legal guardian for the publication of this case report and any accompanying images.A copy of the written consent is available for review by the Editor-in-Chief of this

1
Evolution of necrotizing fasciitis lesion in a preterm neonate: (A) Redness, swelling, and rapid progression to necrosis (B) the discoloration around the umbilicus and two parallel incisions (C) the wound in the healing process.T A B L E 1 Demographic and clinical characteristics of neonates with NF. 18 Streptococcus pyogenes was reported in four cases (5.1%).Pandey et al. also reported Staphylococcus aureus as the most prevalent microbial agent.
ST A B L E 1(Continued) In this The uncommon treatments for NF in neonates.All were performed by the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards.CONSENTWritten informed consent was obtained from the patient's legal guardian for the publication of this case report and any accompanying images.